The object of this study is to use tetrodotoxin as a molecular probe in studies of the voltage-dependent sodium channel in Drosophila melanogaster. We have isolated a mutant which is abnormally sensitive to orally administered tetrodotoxin and have shown that there is a sensitivity difference in both the larval and adult stages of development. The sensitivity difference can also be observed in electrophysiological studies using a dissected larval preparation. We used tetrodotoxin in the concentration range of 10 to the minus 7th power M to 10 to the minus 6th power M and recorded the time required to block nerve conduction. The blockade was both concentration and time dependent, however, at each concentration-time combination tested, the wild-type was less sensitive than the mutant. The tetrodotoxin sensitivity mutation ttxs has been shown to map like a point mutation on the left arm of chromosome 3. Other experiments have shown that the temperature-sensitive paralysis mutant shibire ts has no effects on tetrodotoxin sensitivity.